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Journal of Asian Natural Products... Dec 2023Two new pregnane glycosides ( and ), together with four known ones (- ), were isolated from the roots of Royle ex Wight (Asclepiadaceae). On the basis of detailed...
Two new pregnane glycosides ( and ), together with four known ones (- ), were isolated from the roots of Royle ex Wight (Asclepiadaceae). On the basis of detailed spectroscopic analysis and chemical method, the structures of new compounds were characterized to be metaplexigenin 3---D-cymaropyranosyl- (1→4)--L-diginopyranosyl-(1→4)--D-cymaropyranoside (), metaplexigenin 3---L-diginopyranosyl-(1→4)--D-cymaropyranoside (). All the isolated compounds (-) were tested for their inhibitory activity against the growth of human colon cancer cell lines HCT-116. Compounds and showed significant cytoxicities with IC values of 43.58 µM and 52.21 µM.
Topics: Humans; Cynanchum; Plant Roots; Pregnanes; Glycosides; Molecular Structure
PubMed: 37178131
DOI: 10.1080/10286020.2023.2211550 -
British Journal of Anaesthesia Jul 2024Reductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative...
Reductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative Administration of Dexamethasone and Infection (PADDI) trial assessed the safety of a single preoperative dose of dexamethasone. Surprising to most, in the original report, a single dose of dexamethasone increased the incidence of the secondary outcome chronic postsurgical pain. Was this a chance finding or does dexamethasone increase chronic postsurgical pain? In an attempt to address this question, the PADDI investigators have now analysed this prespecified secondary outcome in two ways: as a substudy published earlier in this Journal, and as a retrospective analysis of the ENIGMA-II chronic pain database in this issue of the Journal. The PADDI investigators have now presented enough data to convince us that indeed a single dose of dexamethasone is safe and effective. However, the increase in chronic postsurgical pain seen in the original PADDI publication highlights the complexities, and the possible immunologic mechanisms, behind the genesis of chronic postsurgical pain. These publications from the PADDI group raise questions about other anti-inflammatory agents we use regularly for long-term postoperative pain management, and highlights the need for well-designed clinical trials to address this critically important patient-centred adverse functional outcome.
Topics: Dexamethasone; Humans; Pain, Postoperative; Chronic Pain; Anti-Inflammatory Agents
PubMed: 38744550
DOI: 10.1016/j.bja.2024.04.011 -
Endocrinology Aug 2023Adverse effects associated with exposure to brominated flame retardants have led to regulations for their use and their replacement with organophosphate esters (OPEs)....
Adverse effects associated with exposure to brominated flame retardants have led to regulations for their use and their replacement with organophosphate esters (OPEs). However, little is known about the impact of OPEs on the adrenal, a vital endocrine gland. Here, we used a high-content screening approach to elucidate the effects of OPEs on H295R human adrenal cell phenotypic endpoints and function. The effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a legacy brominated flame retardant, on H295R cell cytotoxicity, oxidative stress, mitochondria, lysosomes, and lipid droplets were compared with those of 6 OPEs. Most OPEs reduced oxidative stress, increased the numbers of mitochondria, decreased lysosomes, and increased lipid droplets. Two potency ranking approaches, the lowest benchmark concentration/administered equivalent dose methods and Toxicological Prioritization Index analyses, revealed that the triaryl-OPEs (isopropylated triphenyl phosphate [IPPP], tris(methylphenyl) phosphate [TMPP], and triphenyl phosphate [TPHP]) and 1 nontriaryl OPE (tris(1,3-dichloro-2-propyl) phosphate [TDCIPP]) were more potent than BDE-47. The steroidogenic activity of adrenal cells in the presence or absence of forskolin, a steroidogenic stimulus, was determined after exposure to triaryl-OPEs. The basal production of cortisol and aldosterone was increased by IPPP but decreased by TPHP or TMPP exposure; the response to forskolin was not affected by these OPEs. All 3 triaryl OPEs altered the expression of rate-limiting enzymes involved in cholesterol and steroid biosynthesis; CYP11B1 and CYP11B2 were the most prominently affected targets. The OPE chemical-specific effects on cortisol and aldosterone production were best explained by alterations in STAR expression. Thus, the adrenal may be an important target for these endocrine-disrupting chemicals.
Topics: Humans; Flame Retardants; Plasticizers; Aldosterone; Hydrocortisone; Organophosphates; Phosphates; Esters; Phenotype; Environmental Monitoring
PubMed: 37522340
DOI: 10.1210/endocr/bqad119 -
Hypertension Research : Official... Aug 2023Adrenal venous sampling (AVS) is the gold standard for identifying curable unilateral aldosterone excess in primary aldosteronism (PA). Studies have demonstrated the...
Adrenal venous sampling (AVS) is the gold standard for identifying curable unilateral aldosterone excess in primary aldosteronism (PA). Studies have demonstrated the value of steroid profiling through liquid chromatography-tandem mass spectrometry (LC-MS/MS) in AVS interpretation. First, the performance of LC-MS/MS and immunoassay in assessing selectivity and lateralization was compared. Second, the utility of the proportion of individual steroids in adrenal veins in subtyping PA was analyzed. We enrolled 75 consecutive patients with PA who underwent AVS between 2020 and 2021. Fifteen adrenal steroids were analyzed in peripheral and adrenal veins through LC-MS/MS before and after adrenocorticotropic hormone (ACTH) stimulation. Through selectivity index that was based on cortisol and alternative steroids, LC-MS/MS rescued 45% and 66% of failed cases judged by immunoassay in unstimulated and stimulated AVS, respectively. LC-MS/MS identified more unilateral diseases than did immunoassay (76% vs. 45%, P < 0.05) and provided adrenalectomy opportunities to 69% of patients judged through immunoassay to have bilateral disease. The secretion ratios (individual steroid concentration/total steroid concentration) of aldosterone, 18-oxocortisol, and 18-hydroxycortisol were novel indicators for identifying unilateral PA. The 18-oxocortisol secretion ratio of ≥0.785‰ (sensitivity/specificity: 0.90/0.77) at pre-ACTH and aldosterone secretion ratio of ≤0.637‰ (sensitivity/specificity: 0.88/0.85) at post-ACTH enabled optimal accuracy for predicting ipsilateral and contralateral disease, respectively, in robust unilateral PA. LC-MS/MS improved the success rate of AVS and identified more unilateral diseases than immunoassay. The secretion ratios of steroids can be used to discriminate the broad PA spectrum.
Topics: Humans; Aldosterone; Hyperaldosteronism; Hydrocortisone; Tandem Mass Spectrometry; Chromatography, Liquid; Adrenocorticotropic Hormone; Steroids; Retrospective Studies
PubMed: 37311968
DOI: 10.1038/s41440-023-01347-2 -
Archives of Biochemistry and Biophysics Oct 2023Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this...
Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this process. Macrophages, as highly important immune cells, play a significant role in the development of human kidney diseases. But the specific role of macrophages in this process is still unclear. Under different timeline points, we surprisingly found that macrophages had the most dynamic changes in acute kidney injury immune cells. Based on macrophages' functions, they are primarily classified into M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). The polarization of M2 macrophages is closely associated with the seriousness of sepsis-induced kidney injury, but how to modulate their polarization to alleviate sepsis-associated renal damage remains unknown. We discovered that the polarization of M2 macrophages after methylprednisolone injection can significantly alleviate acute kidney injury by reducing secreted cytokine. This study suggests that the proportion of macrophage subtypes can be regulated by methylprednisolone to alleviate acute kidney injury in sepsis to provide a new sight for a clinical to provide a promising strategy for renal injury caused.
Topics: Humans; Methylprednisolone; Kidney; Macrophages; Acute Kidney Injury; Sepsis
PubMed: 37696383
DOI: 10.1016/j.abb.2023.109738 -
Drug Delivery and Translational Research Nov 2023Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to...
Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to its poor bioavailability we further investigated whether nanoparticles (NPs) made of zein protein may constitute a safe and effective choice to incorporate MF. Thus, in this work, we loaded MF into zein NPs aiming to evaluate possible advantages that could result from oral delivery and extend the range of MF application such as inflammatory gut diseases. MF-loaded zein NPs presented an average size in the range of 100 and 135 nm, narrow size distribution (polydispersity index < 0.300), zeta potential of around + 10 mV and association efficiency of MF over 70%. Transmission electron microscopy imaging revealed that NPs had a round shape and presented a smooth surface. The zein NPs showed low MF release in a buffer that mimics the gastric condition (pH = 1.2) and slower and controlled MF release in the intestinal condition (pH = 6.8). The short and intermediate safety of zein NPs was confirmed assessing the incubation against Caco-2 and HT29-MTX intestinal cells up to 24 h. Permeability studies of MF across Caco-2/HT29-MTX co-culture monolayer evidenced that zein NPs modulated MF transport across cell monolayer resulting in a stronger and prolonged interaction with mucus, potentially extending the time of absorption and overall local and systemic bioavailability. Overall, zein NPs showed to be suitable to carry MF to the intestine and future studies can be developed to investigate the use of MF-loaded zein NPs to treat intestinal inflammatory diseases.
Topics: Humans; Mometasone Furoate; Zein; Caco-2 Cells; Nanoparticles; Drug Carriers
PubMed: 37208563
DOI: 10.1007/s13346-023-01367-y -
The Journal of Clinical Endocrinology... Dec 2023
Topics: Humans; Hydrocortisone; Cortisone; Dexamethasone; Saliva; Adrenal Gland Neoplasms
PubMed: 37290037
DOI: 10.1210/clinem/dgad348 -
British Journal of Anaesthesia Jan 2024Two randomised controlled trials have reported a reduction in mortality when adjunctive hydrocortisone is administered in combination with fludrocortisone compared with... (Review)
Review
Two randomised controlled trials have reported a reduction in mortality when adjunctive hydrocortisone is administered in combination with fludrocortisone compared with placebo in septic shock. A third trial did not support this finding when hydrocortisone administered in combination with fludrocortisone was compared with hydrocortisone alone. The underlying mechanisms for this mortality benefit remain poorly understood. We review the clinical implications and potential mechanisms derived from laboratory and clinical data underlying the beneficial role of adjunctive fludrocortisone with hydrocortisone supplementation in septic shock. Factors including distinct biological effects of glucocorticoids and mineralocorticoids, tissue-specific and mineralocorticoid receptor-independent effects of mineralocorticoids, and differences in downstream signalling pathways between mineralocorticoid and glucocorticoid binding at the mineralocorticoid receptor could contribute to this interaction. Furthermore, pharmacokinetic and pharmacodynamic disparities exist between aldosterone and its synthetic counterpart fludrocortisone, potentially influencing their effects. Pending publication of well-designed, randomised controlled trials, a molecular perspective offers valuable insights and guidance to help inform clinical strategies.
Topics: Humans; Glucocorticoids; Fludrocortisone; Hydrocortisone; Shock, Septic; Mineralocorticoids; Receptors, Mineralocorticoid
PubMed: 38030548
DOI: 10.1016/j.bja.2023.10.034 -
Talanta Jan 2024The stressful conditions of today-life make it urgent the timely prevention and treatment of many physiological and psychological disorders related to stress. According... (Review)
Review
The stressful conditions of today-life make it urgent the timely prevention and treatment of many physiological and psychological disorders related to stress. According to the significant progress made in the near future, rapid, accurate, and on-spot measurement of cortisol hormone as a dominant stress biomarker using miniaturized digital devices is not far from expected. With a special potency in the fields of diagnosis and healthcare monitoring, aptamer-mediated biosensors (aptasensors) are promising for the quantitative monitoring of cortisol levels in the different matrices (sweat, saliva, urine, cerebrospinal fluid, blood serum, etc.). Accordingly, this in-depth study reviews the superior achievements in the aptasensing strategies to detect cortisol hormone with the synergism of diverse two/three dimensional nanostructured materials, enzymatic amplification components, and antibody motifs. The represented discussions offer a universal perspective to achieve lab-on-chip aptasensing arrays as future user-friendly skin-patchable electronic gadgets for on-site and real-time quantification of cortisol levels.
Topics: Hydrocortisone; Body Fluids; Biosensing Techniques; Saliva; Aptamers, Nucleotide
PubMed: 37541008
DOI: 10.1016/j.talanta.2023.125010 -
Annals of Clinical Biochemistry Nov 2023The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing's syndrome and the investigation of adrenal...
BACKGROUND
The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing's syndrome and the investigation of adrenal incidentalomas. Despite documented variation in serum cortisol immunoassay performance, little has been published regarding its effect on the ONDST.
AIMS
Assess the performance of three immunoassay platforms (Roche Elecsys II, Abbott Alinity & Siemens Centaur) when compared to a liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
METHODS
Samples ( = 77) sent to the laboratory as part of an ONDST were retrieved prior to disposal, anonymized, and analysed on all platforms. Samples with factors impacting immunoassay analysis quality were excluded. Results were statistically compared to an LC-MS/MS method that previously demonstrated excellent comparability to a candidate reference method.
RESULTS
The Roche gen II showed a mean bias of -2.4 nmol/L and a Passing-Bablok fit of y = -0.9 + 0.97x. This was not affected by sex. The Abbott showed a mean bias -18.8 nmol/L, and a fit of y = -11.3 + 0.88x. This bias was -20.7 nmol/L in females versus -17.2 nmol/L in males. The Siemens had a mean bias of 2.3 nmol/L and a fit of y = 1.4 + 1.07x. This bias was 5.7 nmol/L in males versus -1.0 nmol/L in females.
CONCLUSIONS
Clinicians should be aware of the method-dependent variation that exists within serum cortisol analysis during the ONDSTs. Roche and Siemens aligned more closely with LC-MS/MS while the Abbot may cause a reduction in ONDST sensitivity. This data supports assay-specific cut-offs for the ONDST.
Topics: Male; Female; Humans; Hydrocortisone; Chromatography, Liquid; Adrenal Gland Neoplasms; Tandem Mass Spectrometry; Dexamethasone
PubMed: 37208338
DOI: 10.1177/00045632231179560